it is my ppt lecture on beta blockers

1. Beta adrenergic receptor
antagonists or beta-blockers
PROF. DR. SHAH MURAD
SHAHMURAD65@GMAIL.COM

2.  Beta blockers are prescription medications used to
treat many different conditions, such as high blood
pressure (hypertension) or irregular heart
rhythms (arrhythmias).
 There are numerous different beta blockers
available, and there are several important differences
among the various beta blockers

3. Beta Blockers By Type
 Usually, beta blockers are categorized in a few different
ways.
 Some are "cardioselective" (meaning they are more
likely to affect the heart and blood vessels rather than
other parts of the body), some have "intrinsic
sympathomimetic activity" ( slightly stimulate beta
receptors while also blocking them), and some are
alpha blockers as well as beta blockers.
 some beta blockers fall into more than one category

4. Cardioselective beta blockers
 Acebutolol
 Atenolol
 Betaxolol
 Bisoprolol
 Esmolol
 Nebivolol
 Metoprolol

5. Beta blockers with intrinsic sympathomimetic
activity (ISA)
 Acebutolol
 Carteolol
 Penbutolol
 Pindolol

6. Beta blockrs + alpha-blockade
 CARVEDILOL
 LABETALOL

7. Beta blockers that are non-selective, do not have
ISA, and do not block alpha receptors
 Levobunolol
 Metipranolol
 Nadolol
 Propranolol
 Sotalol
 Timolol

8.  Sotalol is unique among beta blockers in that it also
blocks potassium channels in the heart.

9.  Drugs which inhibit beta adrenergic receptors are
called beta -blocking agents and also beta-blockers.
 They inhibit competitively the beta effects of
endogenous catecholamines.

10.  To understand the consequences of inhibition of beta
receptors , it is necessary to keep in mind the effects
of stimulation of beta receptors.

11. The stimulation of the postsynaptic beta-1 receptors induces:
 cardiac inotropic, chronotropic, dromotropic and
bathmotropic positive effects with increase of cardiac output
and oxygen requirement.
 increase of renin secretion.

12. The stimulation of the postsynaptic beta-2 receptors
induces:
 vasodilation, bronchodilatation, uterine relaxation,
metabolic effects, cardiac inotropic and chronotropic
positive effects but less than those which result from
beta-1 stimulation.
 The stimulation of presynaptic beta-2 receptors
increases noradrenaline release.

13.  The inhibition of beta adrenergic receptors elicits a
decrease or a suppression of the effects of endogenous
catecholamines.
 The effects are more important when endogenous
stimulation is there.
 nhibition of beta receptors has beneficial and adverse
effects

14. Common effects
 The effects of beta-blockers are primarily
cardiovascular.
 They slow heart rate by decreasing the slope of slow
diastolic depolarization and constitute group II of
antiarrhythmic drugs.
 They decrease heart oxygen requirement, which
explains their use in the preventive treatment of
angina pectoris

15.  They decrease, after a latency period, pathological
arterial hypertension, by complex mechanisms,
decrease of cardiac output, inhibition of renin
secretion, and perhaps inhibition of the sympathetic
tone by a central effect.

16.  But they are not true hypotensive agents because
they do not lower, at therapeutic doses, normal
arterial pressure.
 Beta-blockers lower intraocular pressure by
decreasing aqueous humor secretion.

17. Particular effects
 Some beta-blockers have a slight beta-mimetic
activity, called intrinsic sympathomimetic activity or
ISA, whose consequence is that a low beta stimulation
persists.
 They have a high affinity for beta receptors but no or
only a low capacity to activate these receptors.

18.  Being bound to beta receptors, they prevent
endogenous catecholamines from inducing beta
effects and are thus true beta-blockers.

19.  Beta-blockers are classified according their selective
inhibition of beta-1 and/or beta-2receptors.
 Some beta-blockers inhibit at the same time beta-1
and beta-2 receptors, others inhibit only beta-1
receptors.
 The latter are known as cardio-selective.
 It did not appear interesting in therapeutics to
selectively inhibit beta-2 receptors.

20.  In addition to their beta-blocking activity, some beta-
blockers like propranolol and acebutolol, have a
membrane-stabilizing effect which reduces
transmembrane ion exchanges.
 This activity, sometimes called local anesthetic or
antiarrhythmic effect, results from a decrease of the
rate of depolarization by sodium entry.

21.  Labetolol and carvedilol have an alpha-1-blocking
effect, celiprolol a beta-2-agonist effect.
 Propranolol inhibits the transport of iodine in the
thyroid follicle.
 Carvedilol would have, at least in vitro, antioxydant
properties.
 Nebivolol has a NO-mimetic vasodilatator effect.

22. Pharmacokinetic features
 One can distinguish liposoluble and water-soluble
beta-blockers.
 liposoluble beta-blockers like propranolol and
oxyprenolol have common features:

23.  they are quickly and completely absorbed by the digestive
tract.
 they are metabolized in the liver and can undergo an
inactivation known as first metabolism.
 Their ingestion with foods can reduce the importance of first-
pass metabolism and increase their bioavailability.

24. -they are bound at 90% to plasma proteins.
-they have a very great volume of distribution, i.e. they diffuse
readily in tissues.
-they have a rather short duration of action and a short plasma
half-life

25.  water-soluble beta-blockers like atenolol, nadolol
and sotalol have the following properties:
 they are less quite absorbed by the digestive tract and in a
more irregular way
 they are little metabolized by the liver
 they are not very bound to plasma proteins

26.  they are eliminated primarily by the kidney in unchanged form
 they have a restricted volume of distribution
 they have a long plasma half-life

27.  Between these two extremes, very liposoluble beta-
blockers and very water-soluble beta-blockers, there
are intermediate products such as pindolol and
celiprolol.

29. Therapeutic uses
Cardiovascular uses
-angina pectoris: in prevention of attacks
-tachycardia of various origins including those of hyperthyroidism,
in particular the of Gravé's disease where one uses especially
propranolol
-arterial hypertension
-myocardial infarction,
-unstable angina

30. -congestive heart failure, an apparent paradoxical indication.
-Actually, there is in patients with congestive heart failure a
sympathetic overstimulation with an increase of plasma
noradrenaline concentration and a decrease of beta receptors
reactivity.
-Inhibition of beta receptors can, by withdrawing the heart from the
sympathetic overstimulation, improve its activity.

31.  Starting treatment of congestive heart failure by beta-
blockers requires a narrow monitoring.
 The three beta-blockers having shown efficacy in this
therapeutic use are bisoprolol, metoprolol and
carvedilol.
 It is possible that beta-blockers having alpha-1
antagonist effect like carvedilol, are more appropriate
in this indication

32. Other therapeutic uses
prevention of primary and secondary digestive
bleeding in portal hypertension by rupture of
esophageal varices; propranolol is usually used

33. -treatment of migraine, tremor, transitory somatic
symptoms of anxiety, alcohol addiction in which
there appears a beta overstimulation.
-In this case propranolol is usually prescribed
-treatment of glaucoma by ophthalmic solutions,
but they can diffuse into the general circulation
and give adverse effects

34.  Generally dosage of beta-blockers must be gradually
increased at the beginning of the treatment and
gradually decreased at cessation with monitoring
and rest

35. Available preparations
 Beta-blockers are presented in
the form of tablets or of
capsules, some of them in
injectable form are intended for
treatment of acute disorders of
heart rhythm and acute phase
of myocardial infarction.

36.  Beta-blockers, not cardioselective, without Intrinsic
sympathomimetic activity are propranolol, nadolol,
sotalol, tertatolol, timolol, labetolol, carvedilol

37.  Beta-blockers not cardioselective, with ASI.
oxyprenolol ; carteolol and pindolol

38.  Beta1-blockers, cardioselective, without A.S.I.
atenolol ; betaxolol, bisoprolol, metoprolol, esmolol
and nebivolol

39.  Bêta1-blockers, cardioselective, with A.S.I.
Acebutolol, Celiprolol

40.  Beta-blockers combined with a diuretic.
 Many beta-blockers are combined under proprietary
names with a diuretic such as hydrochlorothiazide,
chortalidone, clopamide, amiloride.

41. Ophthalmic solutions of beta-blockers
 for treatment of glaucoma
Beta-blockers in ophthalmic solutions are used in
treatment of glaucoma.
 Beta-blockers presented in ophthalmic formulations
are betaxolol, befunolol, carteolol, metipranolol,
timolol and levobunolol.

42. Adverse effects
 Aggravation of congestive heart failure.
 Congestive heart failure is both an indication and a
contraindication to the use of beta-blockers.

43.  In any case, starting a beta-blocking
treatment cannot be done without a rigorous
analysis of the state of the patient and
necessitates a close monitoring.

44.  Aggravation of bradyarrythmia; bradycardia,
atrioventricular blocks are contraindications to their
prescription.
 Coldness of the extremities , possible aggravation of
arteritis, especially with nonselective beta-blockers
but sometimes also with beta-1 selective.

45.  A ggravation of asthmatic disease, especially with
nonselective beta-blockers - but also sometimes with
beta-1selective blockers.

46.  Worsened risk of anaphylactic shock by partial
inhibition of mechanisms opposed to it

47. Metabolic disorders
 Increase in triglycerides
-increase in cholesterol and the VLDL (very low
density lipoproteins); hypoglycemia in diabetics
-raised risk of developing a type II diabetes after
antihypertensive treatment during several years
by beta-blockers.

48. Various, rare disorders
 immunological disorders, lupus, fibroses.
 Rebound of symptoms at abrupt discontinuation of
beta-blockers >>>>>>>>>>>>> tachycardia,
arterial hypertension, fainting, sweats, nervousness ,
especially risk of angina, myocardial infarction and
sudden death.

49. Diffusion in the body after topical use of ophthalmic
solutions.
 Ophthalmic solutions of beta-blockers have few local
adverse effects, irritation for example, but can have
general adverse effects after systemic diffusion.
 They frequently elicit bradycardia, asthma, in the
elderly
 Elimination in milk >>>>>>>>> Beta-blocker use is
contraindicated during lactation.

50.  In overdoses, accidental or voluntary, beta-blockers
cause hypotension, bradycardia, heart rhythm
disorders and shock.

51.  A drug likely to reduce disorders caused by beta-
blockers is glucagon because it stimulates
adenylcyclase despite the blockade of beta-receptors.

52.  Poisoning by beta-blockers with membrane
stabilizing activity appears more difficult to treat
than that elicited by beta-blockers which do not have
this activity

53. Characteristics of beta-blockers
DRUG SELECTIVITY Partial- Local Lipid Half life
agonist anesthetic solubility
activity effect
Acebutolol B-1 + + Low 3-4 h
Atenolol B-1 - - Low 6-9 h
Esmolol B-1 - - Low 10 min
Carvedilol - - - ? 7-10 h
Labetalol - + + Mod 5h
Metoprolol B-1 - + Mod 3-4 h
Nadolol - - - Low 14-24 h
Pindolol - + + Mod 3-4 h
Propranolol - - + High 4-6 h
Timolol - - - Mod 4-5 h

54. Therapeutic uses of beta blockers

55. Used for HYPERTENSION
 Drugs (atenolol, propranolol, metoprolol, timolol)
 Effect > reduced cardiac out put, reduced renin
secretion

56. Angina pectoris
 Drugs…….propranolol, nadolol
 Effects…… -ve chrn: and –ve ionot: effect

57. Arrhythmia prophylaxis after MI
 Propranolol, metoprolol, timolol
 Effects…….reduced automaticity of all cardiac
pacemakers

58. Supraventricular tachycardias
 Propranolol, esmolol, acebutolol
 Effects…..slowed AV conduction velocity

59. Hepertropic cardiomyopathy
 Propranolol
 Effects…..slowed rate of cardiac contraction

60. Migraine
 Propranolol
 Effects….vasodilation

61. Thyroid storm, thyrotoxicosis
 Propranolol
 Effects….. Reduced cardiac rate & arrhythmogenesis

62. Glaucoma
 Timolol
 Effects ……… reduced secretion of aqueous humor

63. Other drugs used in glaucoma
 PGs
 Cholinomimetics
 Alpha agonists…..adrenaline, dipivefrin
 Alpha-2 selective antagonists…..apraclonidine,
brimonidine
 Diuretics …acetazolamide, dorzolamide